The great beauty of Shaw's book, for me, is that he approaches this topic from a relational perspective, which is aligned with my approach to therapy.

Narcissism can be understood as both traumatic and traumatizing:

The developmental traumas that engender narcissism are transmitted intergenerationally

The central trauma in the genesis of narcissism is chronic, insufficiently repaired failures on the part of caregivers to support the developing child's needs for recognition as a separate subject

The chronic failures of recognition thwart the child's achievement of the capacity for intersubjective relatedness

Most often, these chronic failures arise as a result of narcissistic disturbances in the parent

Pages 3-4

In his long suppressed, extraordinary final paper, "Confusion of Tongues" (Sandor Ferenczi 1933/1980), Ferenczi did much more than point to adult sexualization of children, rather than infantile sexuality and fantasy, as a cause of serious psychological damage the child carries into adulthood. Ferenczi went further, identifying the complex, cumulative emotional trauma the child who is neglected and/or abused experiences in the context of the developmental relationship. He went to describe how parents project their disavowed guilt (and shame) on to the child; and how resentful they were, no matter how well masked, of the child's dependence on them--because of their own disavowed wishes to be the focus of attention and care. He recognized that such parents dissociatively take advantage of the child's instinctive willingness to "introject" the guilt and shame the parent disavows. The child, Ferenczi understood, does this by becoming self-blaming, self-loathing, and self-sacrificing. He becomes the caretaker of the parent, while dissociating the awareness of his own needs, along with his concomitant grief and rage about feeling abandoned and exploited.

Page 4

As with all forms of trauma, dissociation becomes a central survivor mode for the adult child of the traumatizing narcissism. Trauma theorists describe aspect of dissociation as the formation of the "protector/persecutor self" (Howell, 2005; Kalsched, 1996). ... The voice of the protector/persecutor says: "No. Do not believe in yourself, do not hope, do not dare. You'll only be hurt again." As the voice becomes more fearful of retraumatization, it becomes more laden with rejection and hostility, dissociatively identified with and mimicking the traumatizing narcissist caregiver: "You nothing, you loser! No one could or would ever love you, you're disgusting! Give up!"

Page 8

From here on, he spends several pages focused on how the child of narcissistic, traumatizing parents can turn their pain and wounding outward, rather than adopting the dissociative model presented above.

There is a different route taken by some children of traumatizing narcissists--involving externalization, rather than internalization, of the hostile projects of the narcissist parents. People in this group, the externalizers, might come to disdain needs altogether, and imagine that they themselves have no needs, that only others are weak and needy. This sort of person could become fixed in a subjective orientation, paving the way toward manic grandiosity and contempt for others, with a sense of entitlement and self-justification. The same cumulative traumatization to the sense of subjectivity as with the objectified child has taken place, but this child, rather than succumbing to a sense of helplessness and despairing of being able to feel recognized, instead develops as an adult into someone who arranges to wield the power to bestow, or not bestow, recognition upon others. ... Another way to think about this is to posit that the traumatized, thwarted subjective self of this child morphs into a protector self, which succeeds in preventing the internalization of shame and badness. Instead this super-defended self locates badness only in others--never in the self. Rather than persecute the self, this dissociated protector is quick to detect inferiority in others, and able to maintain the sense of superiority quite consistently.

Page 8

The patient who is labeled the deflated, thin-skinned pathological narcissist is usually someone who in development has suffered severe damage to their self-esteem system, and whose self-esteem regulation is therefore inconsistent and precarious, subject to the internal persecution of the split-off protector self. In my view, this person is more aptly deemed a sufferer of cumulative, developmental, post-traumatic stress. These patients are inhabited and often tormented by the ghosts of their traumatizers.

Page 10

The overinflated narcissist is often someone much more like the original Narcissus of Ovid's Metamorphoses, as I understand the Narcissus myth: reveling in being wanted and adored by others, contemptuously deeming no one good enough; reinforcing his grandiose overvaluation of himself by sadistically negating the value and worth of others; and ultimately trapped and destroyed by his delusional obsession with what he perceives to be his own perfection. The narcissist in real life, a myth in his own mind, is so well defended against his developmental trauma, so skillful a disavower of the dependency and inadequacy that is so shameful to him, that he creates a delusional world in which he is a superior being in need of nothing he cannot provide for himself. To remain persuaded of his own perfection, he uses significant others whom he can subjugate. These spouses, siblings, children, or followers of the inflated narcissist strive anxiously to be what the narcissist wants them to be, for fear of being banished from his exalted presence. He is compelled to use those who depend on him to serve as hosts for his own disavowed and projected dependency, which for him signified profound inadequacy and is laden with shame and humiliation. To the extent that he succeeds in keeping inadequacy and dependency external, he can sustain in his internal world his delusions of shame-free, self-sufficient superiority.

Page 10-11

I am especially focusing on a particular type of the predominately overinflated, entitled, grandiose narcissist, and the way in which this person characteristically organizes relationships. I call this person the "traumatizing narcissist." In what I (Shaw, 2010) have previously termed "the pathological narcissist's relational system," I describe the narcissist who seeks hegemony for his subjectivity by weakening and suppressing the subjectivity of the other for the purpose of control and exploitation. The other is then left in grave doubt about the validity and even the reality of their own subjectivity. The sadistic, abusive aspect of narcissism stems from the belief, often held unconsciously, that the separate subjectivity of the other is a threat to the survival, literally and/or figuratively, of one's own subjectivity--and the other must therefore be captured and kept under control.

Page 12

What is most characteristic of the traumatizing narcissist as I am defining him is his compelling need to suppress subjectivity in the other, so that the narcissist's subjectivity is always the exclusively important and only valid focus of any dyad or group. ... Unconsciously, he is using the other to identify with and internalize the disavowed, shameful dependency he projects onto others. In the case of a traumatizing narcissist parent, the child's subjectivity is attacked, suppressed, and shattered. In this situation, the developing child's ability to self-regulate and balance the innate narcissistic tendencies is not just unsupported, but actively derailed by the parent.

Page 12-13

I'm sure that as I get deeper into the book, I will have more to share. Stay tuned.

Ellen Langer was one of the trailblazers in seeing and researching the potential of mindfulness practice as an adjunct to psychotherapy and education. In this week's On Being podcast from NPR, host Krista Tippett speaks with Langer about her work, and about practicing mindfulness with meditation and without yoga.

Social psychologist Ellen Langer's unconventional studies have long suggested what brain science is now revealing: our experiences are formed by the words and ideas we attach to them. Naming something "play" rather than "work" can mean the difference between delight and drudgery. She is one of the early pioneers — along with figures like Jon Kabat-Zinn and Herbert Benson — in drawing a connection between mindlessness and unhappiness, between mindfulness and health. Dr. Langer describes mindfulness as achievable without meditation or yoga — as “the simple act of actively noticing things.”

Like-Minded Conversations

Jon Kabat-Zinn — Opening to Our Lives - Jon Kabat-Zinn has learned, through science and experience, about mindfulness as a way of life. This is wisdom with immediate relevance to the ordinary and extreme stresses of our time — from economic peril, to parenting, to life in a digital age. Esther Sternberg — Stress and the Balance Within - The American experience of stress has spawned a multi-billion dollar self-help industry. Wary of this, Esther Sternberg says that, until recently, modern science did not have the tools or the inclination to take emotional stress seriously. She shares fascinating new scientific insight into the molecular level of the mind-body connection. Richard Davidson — Investigating Healthy Minds - Neuroscientist Richard Davidson is revealing that the choices we make can actually “rewire” our brains. He’s studied the brains of meditating Buddhist monks, and now he’s using his research with children and adolescents to look at things like ADHD, autism, and kindness.

In her new book, Me, Myself, and Why: Searching for the Science of Self, science writer Jennifer Ouellette tackles one of the Big Questions: What makes “me” me? For Ouellette, probing the science of self meant taking personality tests, having her brain scanned and her genome sequenced—even dropping acid. She explains what she learned. (Read an excerpt from her book here.)Produced by Annie Minoff, SciArts Producer Guests

It was intended as a rhetorical question, uttered with an implied
wink and a smirk. The speaker, an ardent skeptic who prided himself on
his rational approach to life, meant no offense. He was merely surprised
to ﬁnd that I, a lover of science, tote a battered key chain embossed
with my astrological sign: Taurus. I’ve carried it with me for 20 years,
like a personal totem.

It was perfectly reasonable for my skeptical inquirer to assume my
key chain says something about me. He was employing cue utilization. We
all rely on cues to make snap judgments when we meet new people, and
those judgments can often be accurate, at least in broad strokes.
Physical attractiveness, race, gender, facial symmetry, skin texture, or
facial expressions and body language are all factors that contribute to
how we form our impressions of people. Those cues may also include our
“stuff”: our choices in fashion, jewelry, tattoos, and key chains all
provide clues about who we are, whether we intend them to do so or not.

Social psychologist Sam Gosling is interested in checking out our
stuff, but not in a creepy, voyeuristic way. He has studied how we ﬁll
our spaces with material things, particularly ofﬁces and bedrooms, to
better understand what those choices say about our personalities. For
instance, certain items function as “conscious identity claims,” things
we choose based on how we wish to be perceived by others—the posters,
artwork, books, or music we display, for example, or the tattoos we ink
onto our bodies. We also ﬁll our personal spaces with “feeling
regulators”: photographs of loved ones, family heirlooms, favorite
books, or souvenirs from travel to exotic locales—anything that serves
to meet some emotional need.

“If you are missing someone, you carry a photo in your wallet, or
propped up next to your computer, or you value a necklace that somebody
gave to you,” Gosling explained. “You do these things to connect to
someone as a sort of proxy, until you see that person again.”

Finally, there is what he terms “unconscious behavioral residue,”
cues we leave behind in our spaces as a result of our habits and
behaviors. A highly conscientious person may alphabetize their books,
while the books of someone who is less conscientious would be more
haphazard and disorganized.

All these conscious and unconscious cues, taken together, paint a
fairly accurate rough sketch of the personality behind them. Gosling’s
research showed that it is possible to scan the objects in someone’s
personal space to make indirect inferences about certain personality
traits. He measured his results using the Big Five personality traits:
openness, conscientiousness, extraversion, agreeableness, and
neuroticism. People who score high on openness, for example, tend to ﬁll
rooms with a greater variety of books and magazines, while those who
score high on conscientiousness tend to have clean, well-lit,
meticulously organized bedrooms.

However, Gosling cautions that this is an imprecise method; we can
misread those cues. We may realize a given item is signiﬁcant in some
way to the owner, but we may not infer correctly the statement that it
is making. Context is key. Position can help distinguish whether an
object is serving as an identity claim or a feeling regulator. If you
walk into someone’s ofﬁce and there is a wedding photo on the desk
facing outward, so it can be clearly seen by visitors, that is likely an
identity claim. However, if the same photo is turned instead to face
the owner, then it likely functions as a feeling regulator, to remind
him or her of a loved one.

That is what happened in my encounter with the skeptic who scoffed
at my choice of key chain. It does say something about me, but he
interpreted it as an identity claim, when in fact it is a feeling
regulator. There is a story behind that key chain, or rather, a singular
person by the name of Nick. We became friends as eager young
twentysomethings in New York City, when we both worked brief stints at
the same legal publisher. Nick was a natural raconteur who could hold a
roomful of dinner guests in rapt attention, usually doubled over in
laughter while he recounted his decidedly Rabelaisian adventures as a
young gay man in Manhattan. He loved good food, good clothes, good
music, good sex, and never shied from offering to buy the next round of
drinks.

But this was at the height of the AIDS epidemic, when an
HIV-positive diagnosis was akin to a death sentence. Over the course of
three years, I watched my friend wither away to a shadow of his former
self as the virus ravaged his immune system, although his wicked sense
of humor and big heart remained intact. Nick even helped me with a
last-minute move on a hot summer day after I was evicted from what
turned out to be an illegal sublet, stopping every now and then to
dramatically wipe the sweat from his brow and announce, “I shouldn’t
even be doing this, you know. I have a terminal illness!” Then he would
grin at my guilty expression and give me a hug to let me know he was
just teasing.

Nick’s own housing situation was even more precarious: Unable to
work as his illness progressed, and unable to sign a lease with a
reputable landlord, he relied on local city charities and the tight-knit
gay community to snag a cluttered, roach-infested basement apartment in
Chelsea whose prior occupant had died. It was dirt cheap, but the
stench of death still hung over the place—likely due to the decaying
rodent corpses trapped behind the sagging walls. Nick hated it and found
it unbearably depressing. Soon he was back in the hospital, and when I
went to visit, he broke down in tears over a game of cribbage and begged
me to help him ﬁnd another option: “Please—I just don’t want to die
there.”

It was exasperating to have to start the housing search all over
again, but how could I refuse my friend just because it would be
inconvenient? It took a good bit of bureaucratic wrangling, but I found
him a small sun-ﬁlled studio. While purchasing a few last-minute
bathroom accessories, I spotted a bright metallic red key chain for sale
at the register, embossed with Nick’s astrological sign: a fellow
Taurus. It seemed like the perfect trinket to hold the key to his new
apartment, a ray of hope after weeks of darkness.

Eight months later, Nick was dead. I’ve carried that key chain ever
since, the only thing I have left from his long-dismantled life. My
totem says nothing about my belief in astrology, although you might be
forgiven for making that assumption. To me, it’s a token of the beloved
friend I lost—the very deﬁnition of a feeling regulator—and a constant
reminder not to take my friends for granted, no matter how busy I
become, because they might be gone sooner than I think. It is also a
symbol of the most valuable thing I ever gave to Nick: a decent place to
die.

Every personal item has a story behind it, at least if it holds any
real meaning for the owner. Cultural historian Mihaly Csikszentmihalyi
has argued that we are attached to old photographs, family heirlooms, or
seemingly insigniﬁcant trinkets precisely because they keep us grounded
in the present, and help us remember the past. In that sense, the
objects with which we ﬁll our homes play a vital role in how we
construct our sense of self. Like Gosling, he lumps such totems into
three distinct categories. There are objects that serve as symbols of
status, or of good taste. There are objects relating to what he terms
“continuity of self” that help construct memory and personality.
Finally, there are objects of relationships, like my Taurus key chain,
that link us to our loved ones and broader social networks. “Without
external props, even our personal identity fades and goes out of focus,”
he writes. “The self is a fragile construction of the mind.”

I might quibble with Csikszentmihalyi’s insistence that the self is a
fragile construct—on the contrary, the self strikes me as surprisingly
robust despite, or perhaps because of, its remarkable ﬂuidity—but his
insights into how we infuse material objects with meaning fall right in
line with Gosling’s research. Gosling found that this phenomenon carries
over into our online identities as well: one can infer quite a bit
about somebody’s personality by perusing his or her website, blog, or
even an e-mail address. (Many Internet hipsters still sneer at those who
use AOL or Hotmail addresses, for example.) We form very different ﬁrst
impressions of someone whose email address is just their ﬁrst and last
name, versus someone who uses the handle “sexyspacekitty69.” Nowhere
does this become more apparent than on Facebook, where we create
detailed personal proﬁles of our likes and dislikes, share links, play
games, take quizzes, and post personal photographs. As of 2011, there
were more than 600 million active users in the United States alone.
Increasingly, our Facebook pages are where we keep our stuff, and our
proﬁles have become gigantic identity claims.

Gosling drew his conclusions from two related studies. In the ﬁrst,
participants took the Big Five personality test, and those results were
compared to the so-called virtual residue (similar to Gosling’s
behavioral residue in the object study) strewn throughout their
respective Facebook proﬁles. Analysis revealed signiﬁcant correlations
between the self-reported Big Five test results and certain personality
traits suggested by the subjects’ Facebook proﬁle pages. Extroverts had
the most friends and interacted far more frequently than introverts,
while those focused, achievement-oriented conscientious types used the
site the least. Those with low scores on conscientiousness were far more
likely to use Facebook to procrastinate.

You might argue that both the answers to the personality tests and
the proﬁle pages were generated by the participants themselves and hence
lacked objectivity. So in the second study, nine undergraduate research
assistants looked at only the archived Facebook proﬁles of the study
participants and rated their personalities based solely on carefully
selected cues: number of photos and photo albums, number of wall posts,
group memberships, total number of friends, and even how many words each
participant used in the “About Me” section.

Once again, there were strong correlations between the proﬁles and
the self-reported assessments: extraversion correlated with the number
of friends and higher levels of online engagement, and openness
correlated with the number of friends. It proved much more difﬁcult to
draw correlations between the cues found on Facebook proﬁles and the
traits of conscientiousness, agreeableness, and neuroticism; the results
were inconclusive. But the two studies aptly demonstrate that your
online and ofﬂine identities overlap on Facebook, and your proﬁle does
reﬂect your most easily observable personality traits. At the end of the
day, Facebook is just one more tool we use for self-veriﬁcation: We
want to be known and understood by others in keeping with how we feel
about ourselves.

Jennifer Ouellette is a science journalist and the author of three previous books. She has written for The Wall Street Journal, The Washington Post, Discover, Salon, and Nature,
among other publications, and her heavily trafficked science and
culture blog, Cocktail Party Physics, is hosted on the website of Scientific American.
She lives in Los Angeles with her husband, Caltech physicist Sean M.
Carroll. Visit her online or follow her on Twitter @JenLucPiquant.

Matsuo Basho (1644–1694) lived his peculiar life on the conviction that art could create an awareness that allowed one to see into and communicate the essence of experience. Throughout his life he searched for the state of being one with the object of his poems, something he believed a poet needed to reach in order to write truthfully. This life-long search brought Basho to wandering. He thought that travelling would lead to a state of karumi (lightness), essential for art. In May 1689, when he was already a renowned poet in Japan, he sold his house and embarked on his greatest trip. Basho travelled light, always on foot and always slowly, looking carefully and deeply. He sought to leave everything behind (even himself) and have a direct experience with the nature around him, and he saw Zen Buddhism and travelling as the way to achieve this. He walked 2000 kilometers around the northern coast of Honshu (Japan’s main island), writing prose and poetry along the way, and compiling it all in a book that changed the course of Japanese literature, The Narrow Road to the Deep North.

We are Pablo Fernández (writer) and Anya Gleizer (painter), the adventurers and artists behind In Basho’s Footsteps. 325 years have passed since Basho began hiking the Narrow Road. This summer, we will retrace his trail, in an effort to come in contact with Basho’s approach to art and travelling. We will hike for three months, camping on the way, travelling as lightly and austerely as possible. We will write and paint along the route, and compile what we produce in an artist’s book. It will be hard, but art avails no compromises. Of course, apart from the physical and mental hardships, there are financial ones (flights and food for three months, and publishing costs). To make the project possible, we have used Kickstarter, a crowdfunding platform. With Kickstarter people are able to fund the projects they like, and receive a reward in exchange (we are giving our backers copies of our book, silk-screen prints and even paintings, depending on the pledge). This is a great way of creating an audience involved in the creation process. We don’t only receive financial support, but also very useful feedback, and we will be able to show our audience how the book is coming together. Because we want our art to reach as many people as possible, we are giving a digital edition of the book to everyone who backs the project with more than $5, before the book is accessible to the general public. Our Kickstarter campaign ends on June 4th. It has been a great success so far: We have already covered the travelling costs and now we are funding the publishing costs. For us, crowd-funding has opened up the traditional obstacles between creators and readers. This summer, with the help of all our supporters, we will retrace Basho’s Footsteps.

Here is another article for the "does a bear shit in the woods" file. OF COURSE social anxiety and PTSD are connected to developmental trauma - almost EVERYTHING we call mental illness is the result of developmental trauma or shock trauma.

On the bright side, at least someone is doing the research and writing the articles - in time, maybe we will stop looking for the magic pill to make it all better and start paying attention to how our children are being raised. If we want to reduce the psychological adaptations we call mental illness, then we need to start with teaching people how to be good nurturing parents (which means helping them deal with their own traumas).

Full Citation:Bishop, M. Rosenstein, D, Bakelaar, S, and Seedat, S. (2014, May 29). An analysis of early developmental trauma in social anxiety disorder and posttraumatic stress disorder. Annals of General Psychiatry; 13:16. doi:10.1186/1744-859X-13-16

Abstract (provisional)

Background The early contributions of childhood trauma (emotional, physical, sexual, and general) have been hypothesized to play a significant role in the development of anxiety disorders, such as posttraumatic stress disorder (PTSD) and social anxiety disorder (SAD). The aim of this study was to assess childhood trauma differences between PTSD and SAD patients and healthy controls, as measured by the Early Trauma Inventory. Methods We examined individuals (N = 109) with SAD with moderate/severe early developmental trauma (EDT) (n = 32), individuals with SAD with low/no EDT (n = 29), individuals with PTSD with EDT (n = 17), and healthy controls (n = 31). The mean age was 34 years (SD = 11). Subjects were screened with the Mini-International Neuropsychiatric Interview (MINI), Liebowitz Social Anxiety Scale (LSAS), Clinician-Administered PTSD Scale (CAPS), and Childhood Trauma Questionnaire (CTQ). Analysis of variance was performed to assess group differences. Correlations were calculated between childhood traumas. Results Although not statistically significant, individuals with PTSD endorsed more physical and sexual childhood trauma compared with individuals with SAD with moderate/severe EDT who endorsed more emotional trauma. For all groups, physical and emotional abuse occurred between ages 6 and 11, while the occurrence of sexual abuse in individuals with PTSD was at 6-11 years and later (13-18 years) in individuals with SAD with moderate/severe EDT. For emotional abuse in all groups, the perpetrator was mostly a primary female caregiver; for sexual abuse, it was mostly a nonfamilial adult male, while for physical abuse, it was mostly a caregiver (male in PTSD and female in SAD with moderate/severe EDT). Conclusions The contribution of childhood abuse to the development of PTSD and SAD and the differences between these groups and other anxiety disorders should not be ignored and attention should be given to the frequency and severity of these events. The relationship of the perpetrator(s) and the age of onset of childhood abuse are also important considerations as they provide a useful starting point to assess impact over the life course. This can, in turn, guide clinicians on the optimal timing for the delivery of interventions for the prevention of PTSD and SAD.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Thursday, May 29, 2014

I heard this story on NPR's All Things Considered the other day coming home from work. I wasn't sure whether to be amazed or to laugh. Everyone sounds so authentic - it must have taken years for them to learn how to sound like that. But maybe I am just hyper-cynical (well, okay, there's no "maybe" about it), and maybe they really are trying to solve the horrendous wealth distribution issues we face today. But I doubt it.

They do have a catchy name, however, with the "inclusive capitalism" thing. Still, the 250 people in the room were worth a combined $30 trillion, roughly one-third of the total investable wealth in the world (like the top 1% of the 1%). It's hard to think they want to give up that power so that the other 99.9% can live safer, healthier, easier lives.

I would love to see these people embrace a compassionate capitalism, instilling some social and relational ethics into the capitalist model.

Below the NPR story is some information from the Inclusive Capitalism Initiative, including a link to their founding blueprint (i.e., mission statement).

Prince Charles talks to Lynn Forester de Rothschild (left), organizer of the Conference on Inclusive Capitalism, and Christine Lagarde, head of the International Monetary Fund, before Tuesday's conference. The 250 corporate and financial leaders who attended control some $30 trillion, about a third of the world's investable assets.
WPA Pool/Getty Images

Talk of economic mobility and the wealth gap is hardly new. From the Occupy movement to President Obama's re-election campaign, income inequality has been in the spotlight for years. Even so, the "inclusive capitalism" conference in London on Tuesday broke new ground. Not because of the conversation, but because of the people having it. The 250 people from around the world invited to attend this one-day conference do not represent "the 99 percent," or even the 1 percent. It's more like a tiny fraction of the 1 percent. "We have $30 trillion of assets under management in the room," says conference organizer Lynn Forester de Rothschild, who runs E.L. Rothschild, a major investment firm she and her husband, of the storied Rothschild banking family, founded in 2003. That amount — $30 trillion — is roughly one-third of the total investable wealth in the world. If money is power, then this is the most powerful group of people ever to focus on income inequality. "If this bulk of capital decides that they are going to invest in companies that aren't only thinking about the short-term profit," says Rothschild, "then we will see corporate behavior change." The titans of commerce and finance didn't necessarily fly to this meeting in London out of a sense of ethics or moral duty, though that may be a motivation for some. For many, says Rothschild, it's a sense of self-preservation. Capitalism appears to be under siege. "It's true that the business of business is not to solve society's problems," she says. "But it is really dangerous for business when business is viewed as one of society's problems. And that is where we are today." Prince Charles kicked off the morning's proceedings. "What is so impressive about today's gathering is that every one of you, ladies and gentlemen, is so well-placed to take the kind of action needed to create a new form of inclusive capitalism," he told the conference. Defining Inclusive Capitalism That phrase, "inclusive capitalism," is deliberately broad. People talked about it as valuing long-term investment over short-term profits. Some mentioned environmental stewardship; others focused on treating workers well. Christine Lagarde, who runs the International Monetary Fund, said it is a way to rebuild trust in the financial system. "So the big question is, how can we restore and sustain trust?" she asked in her keynote speech. "First and foremost, by making sure that growth is more inclusive and that the rules of the road favor the many and not just the few." She said this will be a hard slog, because there will be winners and losers, "and the likely losers are those who have the biggest voice, because they have the largest means." Later in the day, the group heard speeches from former U.S. President Bill Clinton and Bank of England chief Mark Carney. Critics suggest this may all be optics. The conference delegates didn't sign on to a specific action plan, or even publicly endorse a set of values. "I suspect the return on investment in this conference is astonishingly low," says Scott Winship of the Manhattan Institute, a conservative-leaning think tank. "It sort of surprises me that you have a bunch of people in the investment community who view this as having a significant return on investment in some way, whether the return is in people patting them on the back and saying, 'Thanks for caring about us,' or in actual changes to policies." Conference organizer Rothschild says there will be follow-up with all of the delegates, but she made a conscious decision not to ask for any commitments up front. "Even for me," she says laughing, "I thought that would be a little pushy."

* * * * * * * * * *

The Inclusive Capitalism Initiative (ICI) is a non-profit organisation that seeks practical ways to renew capitalism to make it an engine of economic opportunity and shared prosperity through the adoption of inclusive business practices.

The Initiative was originally conceptualised as The Henry Jackson Initiative for Inclusive Capitalism in 2011 by The Henry Jackson Society think-tank in response to the financial crisis, which highlighted the serious dislocations caused by developments in capitalism over the last 30 years: worldwide increases in income inequality, large-scale corporate and financial scandals and the fraying of public trust in business, historically high and persistent unemployment and short-term approaches to managing and owning companies.

Towards a More Inclusive Capitalism, the founding blueprint for the Initiative, was co-authored by a Task Force of British and American business leaders and senior policy makers. The Task Force was co-chaired by Dominic Barton, Global Managing Director, McKinsey & Company, and Lady Lynn Forester de Rothschild, CEO, E.L. Rothschild. The Conference on Inclusive Capitalism: Building Value, Renewing Trust

The Conference on Inclusive Capitalism on 27 May 2014 has been created by The Inclusive Capitalism Initiative in order to bring together global leaders from the top institutional investors, asset managers, corporations, sovereign wealth funds and financial institutions to define concrete steps that all of modern capitalism’s stakeholders can take to renew trust and deliver better social and economic outcomes for all.

This new research from Molecular Brain shows, for the first time, that the gene expression patterns in the schizophrenic prefrontal cortex (PFC) resemble those in the juvenile PFC. This can possibly open new avenues for therapeutic interventions (not with drugs), including some of the Mindsight techniques developed by Dan Siegel that target the medial prefrontal cortex.

Abstract (provisional)

Background Schizophrenia, a severe psychiatric disorder, has a lifetime prevalence of 1%. The exact mechanisms underlying this disorder remain unknown, though theories abound. Recent studies suggest that particular cell types and biological processes in the schizophrenic cortex have a pseudo-immature status in which the molecular properties partially resemble those in the normal immature brain. However, genome-wide gene expression patterns in the brains of patients with schizophrenia and those of normal infants have not been directly compared. Here, we show that the gene expression patterns in the schizophrenic prefrontal cortex (PFC) resemble those in the juvenile PFC. Results We conducted a gene expression meta-analysis in which, using microarray data derived from different studies, altered expression patterns in the dorsolateral PFC (DLFC) of patients with schizophrenia with those in the DLFC of developing normal human brains, revealing a striking similarity. The results were replicated in a second DLFC data set and a medial PFC (MFC) data set. We also found that about half of the genes representing the transcriptomic immaturity of the schizophrenic PFC were developmentally regulated in fast-spiking interneurons, astrocytes, and oligodendrocytes. Furthermore, to test whether medications, which often confound the results of postmortem analyses, affect on the juvenile-like gene expressions in the schizophrenic PFC, we compared the gene expression patterns showing transcriptomic immaturity in the schizophrenic PFC with those in the PFC of rodents treated with antipsychotic drugs. The results showed no apparent similarities between the two conditions, suggesting that the juvenile-like gene expression patterns observed in the schizophrenic PFC could not be accounted for by medication effects. Moreover, the developing human PFC showed a gene expression pattern similar to that of the PFC of naive Schnurri-2 knockout mice, an animal model of schizophrenia with good face and construct validity. This result also supports the idea that the transcriptomic immaturity of the schizophrenic PFC is not due to medication effects. Conclusions Collectively, our results provide evidence that pseudo-immaturity of the PFC resembling juvenile PFC may be an endophenotype of schizophrenia. The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

I Tuesday I shared the Bessel van der Kolk article from the New York Times Magazine. From the same issue is this article on how we are learning to "hack" the nervous system to turn on the immune system and to change brain states. Another recent article, "How the ‘Gut Feeling’ Shapes Fear," identified the vagus nerve as a conduit for body states becoming mind states - the "gut feeling" becomes anxiety when the info reaches the brain.

Mirela Mustacevic, who suffers from rheumatoid arthritis, had a nerve stimulator implanted as part of a medical trial. Her symptoms have lessened significantly.

Credit Sarah Wong for The New York Times

One morning in May 1998, Kevin Tracey converted a room in his lab at the Feinstein Institute for Medical Research in Manhasset, N.Y., into a makeshift operating theater and then prepped his patient — a rat — for surgery. A neurosurgeon, and also Feinstein Institute’s president, Tracey had spent more than a decade searching for a link between nerves and the immune system. His work led him to hypothesize that stimulating the vagus nerve with electricity would alleviate harmful inflammation. “The vagus nerve is behind the artery where you feel your pulse,” he told me recently, pressing his right index finger to his neck.The vagus nerve and its branches conduct nerve impulses — called action potentials — to every major organ. But communication between nerves and the immune system was considered impossible, according to the scientific consensus in 1998. Textbooks from the era taught, he said, “that the immune system was just cells floating around. Nerves don’t float anywhere. Nerves are fixed in tissues.” It would have been “inconceivable,” he added, to propose that nerves were directly interacting with immune cells.Nonetheless, Tracey was certain that an interface existed, and that his rat would prove it. After anesthetizing the animal, Tracey cut an incision in its neck, using a surgical microscope to find his way around his patient’s anatomy. With a hand-held nerve stimulator, he delivered several one-second electrical pulses to the rat’s exposed vagus nerve. He stitched the cut closed and gave the rat a bacterial toxin known to promote the production of tumor necrosis factor, or T.N.F., a protein that triggers inflammation in animals, including humans.“We let it sleep for an hour, then took blood tests,” he said. The bacterial toxin should have triggered rampant inflammation, but instead the production of tumor necrosis factor was blocked by 75 percent. “For me, it was a life-changing moment,” Tracey said. What he had demonstrated was that the nervous system was like a computer terminal through which you could deliver commands to stop a problem, like acute inflammation, before it starts, or repair a body after it gets sick. “All the information is coming and going as electrical signals,” Tracey said. For months, he’d been arguing with his staff, whose members considered this rat project of his harebrained. “Half of them were in the hallway betting against me,” Tracey said.Inflammatory afflictions like rheumatoid arthritis and Crohn’s disease are currently treated with drugs — painkillers, steroids and what are known as biologics, or genetically engineered proteins. But such medicines, Tracey pointed out, are often expensive, hard to administer, variable in their efficacy and sometimes accompanied by lethal side effects. His work seemed to indicate that electricity delivered to the vagus nerve in just the right intensity and at precise intervals could reproduce a drug’s therapeutic — in this case, anti-inflammatory — reaction. His subsequent research would also show that it could do so more effectively and with minimal health risks.Tracey’s efforts have helped establish what is now the growing field of bioelectronics. He has grand hopes for it. “I think this is the industry that will replace the drug industry,” he told me. Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold. “Our idea would be manipulating neural input to delay the progression of cancer,” says Paul Frenette, a stem-cell researcher at the Albert Einstein College of Medicine in the Bronx who discovered a link between the nervous system and prostate tumors.“The list of T.N.F. diseases is long,” Tracey said. “So when we created SetPoint” — the start-up he founded in 2007 with a physician and researcher at Massachusetts General Hospital in Boston — “we had to figure out what we were going to treat.” They wanted to start with an illness that could be mitigated by blocking tumor necrosis factor and for which new therapies were desperately needed. Rheumatoid arthritis satisfied both criteria. It afflicts about 1 percent of the global population, causing chronic inflammation that erodes joints and eventually makes movement excruciating. And there is no cure for it.In September 2011, SetPoint Medical began the world’s first clinical trial to treat rheumatoid-arthritis patients with an implantable nerve stimulator based on Tracey’s discoveries. According to Ralph Zitnik, SetPoint’s chief medical officer, of the 18 patients currently enrolled in the ongoing trial, two-thirds have improved. And some of them were feeling little or no pain just weeks after receiving the implant; the swelling in their joints has disappeared. “We took Kevin’s concept that he worked on for 10 years and made it a reality for people in a real clinical trial,” he says.Conceptually, bioelectronics is straightforward: Get the nervous system to tell the body to heal itself. But of course it’s not that simple. “What we’re trying to do here is completely novel,” says Pedro Irazoqui, a professor of biomedical engineering at Purdue University, where he’s investigating bioelectronic therapies for epilepsy. Jay Pasricha, a professor of medicine and neurosciences at Johns Hopkins University who studies how nerve signals affect obesity, diabetes and gastrointestinal-motility disorders, among other digestive diseases, says, “What we’re doing today is like the precursor to the Model T.”The biggest challenge is interpreting the conversation between the body’s organs and its nervous system, according to Kris Famm, who runs the newly formed Bioelectronics R. & D. Unit at GlaxoSmithKline, the world’s seventh-largest pharmaceutical company. “No one has really tried to speak the electrical language of the body,” he says. Another obstacle is building small implants, some of them as tiny as a cubic millimeter, robust enough to run powerful microprocessors. Should scientists succeed and bioelectronics become widely adopted, millions of people could one day be walking around with networked computers hooked up to their nervous systems. And that prospect highlights yet another concern the nascent industry will have to confront: the possibility of malignant hacking. As Anand Raghunathan, a professor of electrical and computer engineering at Purdue, puts it, bioelectronics “gives me a remote control to someone’s body.”Despite the uncertainties, in August, GlaxoSmithKline invested $5 million in SetPoint, and its bioelectronics R. & D. unit now has partnerships with 26 independent research groups in six countries. Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer. “This is not a one-trick pony.”Kevin Tracey, who is 56, came to bioelectronics because of two significant deaths. The first occurred when he was in preschool. He was 5 when his mother died as a result of an inoperable brain tumor. Shortly after the funeral, Tracey found his maternal grandfather, a professor of pediatrics at Yale, alone in his den. “I climbed onto his lap and asked what happened,” Tracey says. “He explained that surgeons tried to take it out but couldn’t separate the brain-tumor tissue from the normal neurons. I remember saying to him, ‘Somebody should do something about that.’ That was when I decided to be a neurosurgeon. I wanted to solve problems that were insolvable.”Tracey’s second formative experience took place in May 1985. Having trained for neurosurgery at Cornell, he was on rotation for his residency in the emergency room at New York Hospital when an 11-month-old baby girl named Janice arrived in an ambulance with burns covering 75 percent of her body. Her grandmother was cooking when she tripped and doused Janice with a pot of boiling noodles. After three weeks in the burn unit recovering from skin grafts, Janice appeared to stabilize. Tracey joined Janice’s family to celebrate her first birthday in her hospital room. Janice was upbeat, smiling and giggling. The next day, she was dead.“I was haunted by her case,” Tracey says. When the autopsy report was inconclusive, Tracey redirected his energy into medical research, specifically inflammation related to sepsis, which he believed contributed to Janice’s unexpected death. Sepsis occurs when the immune system goes into overdrive, producing a potentially lethal inflammatory response to fight a severe infection. At the time of her death, however, Janice did not have an infection. It took another year to figure out that it was an overproduction of tumor necrosis factor — the catalyst for inflammation — that caused Janice’s septic shock, though her death remains a mystery.

Kevin Tracey, a neurosurgeon, studies the effects of stimulating nerves with electricity to fight disease. Credit Katherine Wolkoff for The New York Times

“Her brakes had failed,” Tracey says. “She made too much T.N.F. The obvious question was, why?” He credits Linda Watkins, a neuroscientist at the University of Colorado, Boulder, for furnishing the pivotal clue. In the mid-1990s, Watkins was exploring possible neural connections between the brain and the immune system in rats by injecting them with cytokines — molecules that, like tumor necrosis factor, contribute to inflammation — to cause fevers. But when she cut their vagus nerves, the fever never materialized. Watkins concluded that the vagus nerve must be the conduit through which the body signals the brain to induce fever.Tracey followed her lead by giving mice a toxin known to cause inflammation and then dosing them with an anti-inflammatory drug he had been investigating. “We injected it into their brains in teeny amounts, too small to get into their bloodstream,” he says. The drug did what it was supposed to do: It halted the production of tumor necrosis factor in the brain. Surprisingly, it also halted the production of tumor necrosis factor in the rest of the body. When Tracey cut the vagus nerve, however, the drug had no effect in the body.“That was the eureka moment,” he says. The signal generated by the drug had to be traveling from the brain through the nerve because cutting it blocked the signal. “There could be no other explanation.”Tracey then wondered if he could eliminate the drug altogether and use the nerve as a means of speaking directly to the immune system. “But there was nothing in the scientific thinking that said electricity would do anything. It was anathema to logic. Nobody thought it would work.”After that first surgery on the rat in 1998, Tracey spent 11 years mapping the neural pathways of tumor-necrosis-factor inflammation, charting a route from the vagus nerve to the spleen to the bloodstream and eventually to mitochondria inside cells. “We now know more about this electrical circuit to treat [inflammation] than is known about some clinically approved drugs,” Tracey says.By 2009, SetPoint felt ready to test Tracey’s work on people with rheumatoid arthritis, and Ralph Zitnik was approached about joining thecompany. “It was nuts,” Zitnik told me. “Sticking something on the vagusnerve to take away R.A.? People would think it’s witchcraft.” Zitnik’s background was in pharmaceuticals; at Amgen, he contributed to the development of Enbrel, a rheumatoid-arthritis drug that had $4.7 billion in sales last year, which made it No. 7 on the industry’s best-seller list. But the more he talked with Tracey and pored over the research, the more he said to himself: “There is good science behind this. I thought, This could work.”

SHOCK TREATMENT

During a 20-minute operation, a neurosurgeon will slide SetPoint Medical’s bioelectronic implant onto the vagus nerve on the left side of a patient’s neck, and then snap on an outer housing called the Pod to hold the device in place. Once the implant is activated, electrical impulses transmitted from the implant will communicate directly with immune cells in the spleen and the gastrointestinal tract, inducing them to reduce the production of cytokines — molecules that are involved in inflammation. To recharge the device’s batteries and update its software, patients and physicians will use an iPad app to control a wearable collar that transmits power and data wirelessly through the skin.

Zitnik’s first task at SetPoint was to recruit a lead scientist to set up a clinical trial. Many scientists in the United States and Europe were hesitant to do it, he says, but eventually he hired Paul-Peter Tak, a well-regarded immunologist and rheumatologist based at the Academic Medical Center, the University of Amsterdam’s teaching hospital. “He was a forward-thinking person willing to try an unconventional approach like this,” Zitnik says. Tak in turn hired Frieda Koopman, who was working on her Ph.D. in rheumatology at A.M.C., to find potential patients in the Netherlands and elsewhere in Europe.The day after an article about the planned trial appeared in a Dutch newspaper, Koopman’s office got more than a thousand calls from rheumatoid-arthritis patients begging to participate. “We never saw that coming,” Koopman says. “We thought we might get one or two patients to join, and wouldn’t that be nice.” Invasive surgery was involved, after all. Koopman’s team returned almost every call and selected several subjects based on what medications they had tried and the severity of the pain and swelling in their joints. Over the next two years, her team continued to enroll new patients.The subjects in the trial each underwent a 45-minute operation. A neurosurgeon fixed an inchlong device shaped like a corkscrew to the vagus nerve on the left side of the neck, and then embedded just below the collarbone a silver-dollar-size “pulse generator” that contained a battery and microprocessor programmed to discharge mild shocks from two electrodes. A thin wire made of a platinum alloy connected the two components beneath the skin. Once the implant was turned on, its preprogrammed charge — about one milliamp; a small LED consumes 10 times more electricity — zapped the vagus nerve in 60-second bursts, up to four times a day. Typically, a patient’s throat felt constricted and tingly for a moment. After a week or two, arthritic pain began to subside. Swollen joints shrank, and blood tests that checked for inflammatory markers usually showed striking declines.Koopman told me about a 38-year-old trial patient named Mirela Mustacevic whose rheumatoid arthritis was diagnosed when she was 22, and who had since tried nine different medications, including two she had to self-inject. Some of them helped but had nasty side effects, like nausea and skin rashes. Before getting the SetPoint implant in April 2013, she could barely grasp a pencil; now she’s riding her bicycle to the Dutch coast, a near-20-mile round trip from her home. Mustacevic told me: “After the implant, I started to do things I hadn’t done in years — like taking long walks or just putting clothes on in the morning without help. I was ecstatic. When they told me about the surgery, I was a bit worried, because what if something went wrong? I had to think about whether it was worth it. But it was worth it. I got my life back.”In February, I met Moncef Slaoui, Glaxo’s chairman of Global Research and Development, at one of the company’s 16 facilities he oversees worldwide, this one in King of Prussia, Pa. Slaoui, who is 55 and has a Ph.D. in molecular biology and immunology, was instrumental in developing the first malaria vaccine and is considered one of the most influential executives in the pharmaceutical industry.“When Kris came to me in early 2012 with this idea of vagus nerve stimulation,” Slaoui told me, “I was like: C’mon? You’re gonna give a shock and it changes the immune system? I was very skeptical. But finally I agreed to visit Kevin’s lab. I wanted the data, the evidence. I don’t like hot air.” He went to Tak, the lead scientist for the trials. “I asked him, ‘Paul-Peter, is it really real?’ ”

SetPoint Medical’s new neural implant (currently being tested on animals). Credit Katherine Wolkoff for The New York Times

After getting an endorsement from Tak, who is now Glaxo’s global head of immuno-inflammation research, Slaoui committed to financing SetPoint. The investment was modest, though, because he felt that Tracey’s device was “just a starting point. It was still very broad — you touch the vagus nerve, you touch most of your viscera. We had wanted something very specific.” What he didn’t want was “the bulldozer approach” that characterizes already existing stimulators for treating Parkinson’s, chronic pain and epilepsy. (Pacemakers differ because they stimulate muscle, not nerves.) These devices are indiscriminate, blasting electricity into billions of neurons and hoping for the best. As Slaoui saw it, SetPoint’s stimulator was a primitive forerunner to “a device that reads your electrical impulses and sees when something is wrong, then corrects what needs correcting.”In 2006, Slaoui continued, “when I became chairman of R. & D., R. & D. was a liability to this company. We were spending lots of money and not producing new molecules for new medicines. I had to acknowledge that the current way of doing R. & D. wasn’t likely to be successful.” Four years later, Slaoui put together a 14-member think tank and discussed, among other topics, the Human Brain Project. The multinational endeavor, directed by the neuroscientist and Fulbright scholar Henry Markram, at the Swiss Federal Institute of Technology in Lausanne, is trying to create a computer simulation of the human brain. That got Slaoui “thinking about electrical signaling, an opportunity to make medicine — a therapeutic intervention — that’s super highly specific in terms of its geographic position. I’m going to go to the nerve that goes to your kidney and nowhere else, and only to your left kidney, and to a particular area of the left kidney.”That degree of precision would address one of Slaoui’s major criticisms of conventional drugs: They flood the body, and then doctors have to hope that they will perform only where they’re supposed to. “It is really difficult to design a molecule that will only interact where you want it, because it goes everywhere.” The upshot, usually: side effects.Bioelectronics could potentially eliminate those, as well as the costly redundancy involved in the drug-discovery process, in which every promising molecule must be independently evaluated. “There is very little that is transposable from one molecule to the next,” Slaoui said. “You have to redo everything.” Bioelectronics attracted him, he says, because “95 percent of the hardware is the same,” no matter what disease it treats.So Slaoui found himself working for a drug company while devoting himself to the idea of treating illness without drugs. In July 2012, he and Famm toured Markram’s facilities in Lausanne. There Markram showed them a 3-D digital visualization on a giant screen of 100,000 synapses actively firing in a mouse brain.At that moment, Famm says, he and Slaoui realized they were “biting off too much.” Slaoui and Famm concluded that starting with the brain — which seemed logical, given that it’s the body’s C.P.U. — could take decades to yield viable treatments. The human brain’s circuitry, with 100 billion neurons, seemed far too complex. “Why don’t we just skip the brain and go straight to the organs?” Slaoui suggested.Right then, Slaoui said, “we decided to focus on the peripheral nervous system.” The peripheral nerves link the brain and spinal cord (the central nervous system) to the organs and limbs. Rather than try to fathom the brain — a black box, basically, with its 100 trillion neural connections — Slaoui proposed that they put “an interface between a nerve and the organ with an electrical device.” To eavesdrop on a telephone call, his thinking went, you don’t tap into the switching center and search for the conversation. You go to the line nearest the caller’s location. Compared with the brain, the cablelike bundles that are the peripheral nerves contain vastly fewer fibers — hundreds versus billions.

When I joined Famm in Philadelphia in February, he referred to his role as Glaxo’s bioelectronics chief as “like being a missionary.” Famm, who lives in London, was in the U.S. to attend half a dozen meetings with bioelectronics researchers. His challenge is coaxing those from disparate disciplines to embrace a singular vision. Whereas drug discovery primarily involves like-minded thinkers — molecular biologists, chemists, geneticists — bioelectronics calls for alliances between experts in fields that in many cases have little to do with medicine — nanotech, optics, electrical engineering, materials science, computer programming, wireless networking and data mining. At the moment, Famm is focused on getting what he called a “transdisciplinary” group of scientists to agree on how to solve two key technical challenges.The first is shrinking the hardware. It must be small enough to attach to virtually any nerve yet still have enough battery power and circuitry to run algorithms that generate the patterns of electrical impulses needed to treat various diseases. At the Charles Stark Draper Laboratory in Cambridge, Mass., we met with a team working on miniaturization.Draper is best known for internal navigation systems that guide things like ballistic missiles and spaceships. Bryan McLaughlin, who directs bioelectronics development at Draper, showed me the latest prototype mock-up — a dime-size implant. It’s small, he said, but not nearly small enough. McLaughlin wants to get its electrodes, microprocessor, battery and a wireless transmitter into a device no larger than a jelly bean. “It’s also important to make it closed-loop, with the ability to read and write to the nervous system.” The goal, in other words, is to end up with something that can continuously monitor a patient and then dispense bioelectronic therapy as needed.The second challenge is devising a method to make sense of signals emanating simultaneously from hundreds of thousands of neurons. Accurate recording and analysis are essential to bioelectronics in order for researchers to identify the discrepancies between baseline neural signals in healthy individuals and those produced by someone with a particular disease. The conventional approach to recording neural signals is to use tiny probes with electrodes inside called patch clamps. A prostate-cancer researcher, for example, could attach patch clamps to a nerve linked to the prostate in a healthy mouse and record the activity. The same thing would be done with a mouse whose prostate had been genetically engineered to produce malignant tumors. Comparing the output from both might allow the researcher to determine how the neural signals differ in cancerous mice. From such data, a corrective signal could be programmed into a bioelectronic device to treat the cancer.But there are drawbacks to using patch clamps. They can sample only one cell’s activity at a time, and therefore fail to gather enough data to see the big picture. As Adam E. Cohen, who teaches chemistry and physics at Harvard, puts it, “It’s like trying to watch an opera through a straw.”Cohen, an expert in an emerging field called optogenetics, thinks he can overcome the limitations of the patch clamps. His research is trying to use optogenetics to decipher the neural language of disease. “Getting patch clamps into a single [neuron] is extremely slow and laborious — about an hour per cell,” Cohen told me when I visited his lab recently. “The bigger problem is that [neural] activity comes not from the voices of individual neurons but from a whole orchestra of them acting in relation to each other. Poking at one at a time doesn’t give you the global view.”Optogenetics arose out of a series of developments in the 1990s. Scientists knew that proteins, called opsins, in bacteria and algae generated electricity when exposed to light. Optogenetics exploits this mechanism. Opsin genes are inserted into the DNA of a harmless virus, which is then injected into the brain or a peripheral nerve of a test subject. By choosing a virus that prefers some cell types over others, or by altering the virus’s genetic sequence, researchers can target specific neurons — cold- or pain-sensing, for example — or regions of the brain known to be responsible for certain actions or behaviors. Next, an optical fiber — a spaghetti-thin glass cable that transmits light from its tip — is inserted through the skin or skull to the site of the virus. The fiber’s light activates the opsin, which in turn conducts an electrical charge that forces the neuron to fire. Researchers have already controlled mouse behavior with optogenetics — inducing sleep and aggression on command.Before opsins can be used to activate neurons involved in specific ailments, however, scientists must determine not only which neurons are responsible for a particular disease but also how that disease communicates with the nervous system. Like computers, neurons speak a binary language, with a vocabulary based on whether their signal is on or off. The specific sequence, interval and intensity of these on-off shifts determine how information is conveyed. But if each disease can be thought of as speaking its own language, then a translator is needed. What Cohen and others recognized was that optogenetics can do that job. So Cohen reverse-engineered the process: Instead of using light to activate neurons, he used light to record their activity.Cohen showed me his “Optopatch” machine. It consisted of red and blue lasers, mirrors, lenses, a high-speed digital camera, a video projector, a microscope and several quiet cooling fans. After he turned it on, a postdoc fellow who works in his lab, Shan Lou, inserted a petri dish under its microscope. The dish contained 11 live neural cells from mice, harvested from dorsal-root ganglia, which relay sensory input to the brain. Lou added a few drops of capsaicin extract, the irritant in pepper spray, and then turned the camera on for 14 seconds. In that brief period, it snapped 7,000 frames, totaling 12 gigabytes of data. To analyze it, Cohen had written software that searches for patterns by employing techniques developed for digital voice and face recognition. “We also use algorithms and optical tricks derived from astrophysics,” Cohen said. Seconds later, an analysis appeared on Lou’s computer screen. Three of the 11 cells had been identified as firing in response to the capsaicin, indicating that they were pain-sensing neurons. It would have taken Cohen more than a day to record and make sense of that cellular information with a patch clamp. This sort of effort was a step, he said, “toward imaging large numbers of neurons in parallel, hundreds, perhaps thousands.”Cohen is collaborating with Ed Boyden, a professor of neuroscience at M.I.T. and a pioneer in optogenetics, to develop the so-called closed-loop implant envisioned by Bryan McLaughlin at Draper Labs. Optogenetics, Boyden told me, enables him to “aim light at some subset of cells [without] activating all the stray cells nearby.”Opsins might point the way to future treatments for all kinds of diseases, but researchers will most likely have to develop bioelectronic devices that don’t use them. Using genetically engineered viruses is going to be tough to get past the F.D.A. The opsin technique hinges on gene therapy, which has had limited success in clinical trials, is very expensive and seems to come with grave health risks.Cohen mentions two alternatives. One involves molecules that behave like opsins; another uses RNA that converts into an opsin-like protein — because it doesn’t alter DNA, it doesn’t have the risks associated with gene therapy. Neither approach is very far along, however. And “you still face the problem of getting the light in,” he says. Boyden is developing a brain implant with a built-in laser, but Cohen believes an external light source is more likely for most bioelectronics applications.Surmounting these sorts of technical hurdles “might take 10 years,” Famm figures. That seems somewhat optimistic if you consider Glaxo’s investment so far in bioelectronics. Melinda Stubbee, the company’s director of communications, says it has spent roughly $60 million in the area, a pittance compared with its $6.5 billion in total R. & D. expenditures in 2013. Slaoui, defending the number, said, “Funding of R. & D. is like an investment” — money only flows toward bankable ideas. While he thinks the area shows promise, he seems to want independent researchers to do the legwork before Glaxo buys in further.At one point, Famm referred to detractors who say bioelectronics is “too risky, will take too long and is maybe even a bit bonkers.” In trying to find some of them, I contacted a number of financial analysts who track Glaxo and the pharmaceutical industry. One, Mark Clark, at Deutsche Bank, said to me in an email: “I know next to nothing about this early-stage technology! I am prepared to bet you will not find a single Glaxo analyst that knows anything about this! Research technologies were a vogue thing to be expert on in the ‘90s and tech-bubble years, but we only care about drugs that are actually in the clinical pipeline these days, not how they get there — to be brutally blunt!”In short, the fledgling bioelectronics industry is nowhere near mature enough for analysts to make meaningful estimates about its revenue potential. But people like Clark will certainly begin paying closer attention if bioelectronics starts to capture even a sliver of the lucrative pharmaceutical market. Drug sales for rheumatoid arthritis alone were $12.3 billion in 2012. That looks like a big opportunity to an outfit like SetPoint.Yet if large numbers of patients someday choose bioelectronics over drugs, another issue awaits resolution: security. Bioelectronics devices will feature wireless connectivity so they can be fine-tuned and upgraded, “just like the software on your iPhone,” Famm says. And wireless means hackable, an unsettling fact that worries two experts on medical-device security: Niraj Jha, a professor of electrical engineering at Princeton University, and Anand Raghunathan, who runs the Integrated Systems Laboratory at Purdue.Fears of medical devices being hacked aren’t new. In 2007, Dick Cheney’s cardiologist disabled the wireless functionality in the former vice president’s defibrillator to prevent terrorists from trying to stop hisheart. Jha and Raghunathan, along with the lead author, Chunxiao Li, detailed how this might be accomplished in a seven-page paper they wrote, “Hijacking an Insulin Pump,” published in June 2011. The paper described a hack they performed in their lab using inexpensive, off-the-shelf hardware.According to Jha and Raghunathan, there are no known cases of malicious attacks on medical devices. Nevertheless, Raghunathan says, “Society should be warned about these possibilities.” The Department of Homeland Security is no doubt worried, addressing the potential threat in an alert it issued last June. In August, the F.D.A. offered guidelines to medical-device manufacturers, recommending “wireless protection” to reduce “risks to patients from a security breach.” Whether bioelectronics developers do anything to thwart hacking (the F.D.A. guidelines are not mandatory) may ultimately depend on whether Jha and Raghunathan’s fears are realized.Draper’s McLaughlin doesn’t dismiss these concerns but notes that there is no “incentive for device companies to do anything about security.” He adds: “Nobody has been sued. No patient has died. But the first event that occurs with one of these devices — companies will jump on it and create secure platforms.”SetPoint’s chief technology officer is Mike Faltys, a medical engineer who was integral to designing the modern cochlear implant. Faltys worked for six years out of his garage, first re-engineering an existing electrical stimulator, used to stop seizures, that became the device implanted in patients in SetPoint’s trial, and more recently finishing a significantly more advanced implantable unit that he calls “the microregulator.”Housed in a pod shaped like a hot-dog bun and the size of a multivitamin, the microregulator is entirely self-contained — onboard battery, microprocessor and electrodes are integrated into a single unit. It can be wirelessly recharged, and adjusted and updated with an iPad app. The surgery to clamp it onto the vagus nerve will take about 20 minutes, and once in place, it will provide pain relief to a rheumatoid-arthritis patient for a decade or more before it needs servicing.On one occasion during my travels with Famm, I got to hold SetPoint’s newfangled microregulator. For now, it’s only capable of transmitting very crude signals to communicate with the nervous system — more like grunts and groans rather than the precise vocabulary that Slaoui envisions for bioelectronic therapies. Even so, the microregulator felt elegant and powerful and promising in my palm. “A patient gets a device like this implanted once for one disease, and they’re done,” Tracey says. “No prescriptions, no medicines, no injections. That’s the future.That’s what gets me out of bed in the morning.”

Michael Behar writes about science and the environment. His work has appeared in “The Best American Travel Writing” and “The Best American Science and Nature Writing.”